Anti-Tuberin antibody [Y320] (ab32554)

Function

In complex with TSC1, inhibits the nutrient-mediated or growth factor-stimulated phosphorylation of S6K1 and EIF4EBP1 by negatively regulating mTORC1 signaling. Acts as a GTPase-activating protein (GAP) for the small GTPase RHEB, a direct activator of the protein kinase activity of mTORC1. Implicated as a tumor suppressor. Involved in microtubule-mediated protein transport, but this seems to be due to unregulated mTOR signaling. Stimulates weakly the intrinsic GTPase activity of the Ras-related proteins RAP1A and RAB5 in vitro. Mutations in TSC2 lead to constitutive activation of RAP1A in tumors.

Tissue specificity

Liver, brain, heart, lymphocytes, fibroblasts, biliary epithelium, pancreas, skeletal muscle, kidney, lung and placenta.

Involvement in disease

Defects in TSC2 are the cause of tuberous sclerosis type 2 (TSC2) [MIM:613254]. TSC2 is an autosomal dominant multi-system disorder that affects especially the brain, kidneys, heart, and skin. It is characterized by hamartomas (benign overgrowths predominantly of a cell or tissue type that occurs normally in the organ) and hamartias (developmental abnormalities of tissue combination). Clinical symptoms can range from benign hypopigmented macules of the skin to profound mental retardation with intractable seizures to premature death from a variety of disease-associated causes.
Defects in TSC2 are a cause of lymphangioleiomyomatosis (LAM) [MIM:606690]. LAM is a progressive and often fatal lung disease characterized by a diffuse proliferation of abnormal smooth muscle cells in the lungs. It affects almost exclusively young women and can occur as an isolated disorder or in association with tuberous sclerosis complex.

Sequence similarities

Contains 1 Rap-GAP domain.

Post-translational
modifications

Phosphorylation at Ser-1387, Ser-1418 or Ser-1420 does not affect interaction with TSC1.
Phosphorylation at Ser-939 and Thr-1462 by PKB/AKT1 is induced by growth factor stimulation.

Cellular localization

Cytoplasm. Membrane. At steady state found in association with membranes.

Alternative names

Database links